title: [Racemates and enantiomers of basic, substituted 5-phenylhydantoins, synthesis and anti-arrhythmic action].
abstract: The racemates and the enantiomers of 5-phenylhydantoins with basic substituents in 5-position are synthesized on two different routes via the Bucherer-Bergs-reaction. Using lanthanide-shift-reagents the enantiomeric excess for the enantiomers of 3-methyl-5-morpholinomethyl-5-phenylhydantoin (3a) and 3-methyl-5-phenyl-5-(2-phthalimidoethyl)-hydantoin (6a) is found to be more than 98%. The enantiomers of 4d, 5b, 6b, 7a, and 7b, derived from 3a and 6a, possess the same optical purity. The racemates and the enantiomers of 3a, 4d and 5b were tested at atrium of rat hearts on their antiarrhythmic activity. At the right atrium (+)-3a, (+)-4d, and (+)-5b reduce the spontaneous frequence dependent on the dosis. At the left atrium the enantiomers of 3a and 4d show a negative inotropic action (+)-3a is 4.1, (+)-4d is 1.5 more active as the corresponding (-)-enantiomers. Compound (+)-4d exceeds the reference substance diphenylhydantoin by the factor 1.3.
authors.affiliation: Fachrichtung Pharmazeutische Chemie, Universität des Saarlandes, Saarbrücken, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Knabe
authors.forename: J
authors.initials: J
authors.lastname: Baldauf
authors.forename: A
authors.initials: A
authors.lastname: Ahlhelm
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010672:Phenytoin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
chemical_list: D000889:Anti-Arrhythmia Agents; D010672:Phenytoin
vernacular_title: Razemate und Enantiomere basisch substituierter 5-Phenylhydantoine, Synthese und antiarrhythmische Wirkung.